The global regulator CodY responds to oxidative stress by the regulation of glutathione biosynthesis in Streptococcus thermophilus.

CodYst is a global transcriptional regulator that modulates the metabolic network in Streptococcus thermophilus ST2017. In this study, experimental data showed that the cell survival of the codYst defective mutant obviously declined at the presence of 10 mM H2O2, suggesting CodYst was involved in response to the oxidative stress. To investigate this phenomenon, transcriptome analysis and real time-quantitative PCR were performed and the results indicated that the transcriptional level of a bifunctional glutathione synthetase gene (gshF) was downregulated by about 3-fold in the codYst defective mutant, along with a decrease by 20% of the glutathione yield compared with the wild-type in minimal chemical defined medium, whereas half of the viable cells remained after H2O2 challenge. In vitro gel shift assays showed that the purified CodYst could bind to the promoter region of gshF, with a conserved CodYst box, confirming the regulation of CodYst on the gshF gene. To our knowledge, this is first report of CodYst in response to oxidative stress mediated by the regulation of gshF in S. thermophilus.